Photoallergic contact dermatitis from benzydamine presenting mainly as lip dermatitis

BACKGROUND: Benzydamine, a non-steroidal anti-inflammatory drug (NSAID) in use for more than four decades, has been reported to cause photosensitivity. OBJECTIVES: To study the results of photopatch testing to benzydamine and the clinical features of the dermatitis during a 3-year period (2006-2008). PATIENTS AND METHODS: During this period, 74 patients with photodermatoses were photopatch tested with an extended baseline series of allergens including benzydamine and in suspicious cases, with drugs that contain it. Test sites were irradiated on D2 with 5 J/cm(2) and readings were performed on D2 and D4. RESULTS: Ten patients (six females/four males), aged 21-84 years (mean 64.9) had a positive photopatch test to benzydamine [1-5% petrolatum (pet.) from Bial-Aristegui] and to drugs that contain it (Tantum verde oral solution and Momen gel). Nine patients had lower lip cheilitis and one lichenified eczema on photo-exposed sites. CONCLUSION: Photosensitivity from both topical and systemic benzydamine has been occasionally described, mainly in southern Spain. Despite its widespread use and its known photosensitizing capacity, photoallergic contact dermatitis from benzydamine is probably underdiagnosed as the clinical presentation of mainly the lip and chin is not typical of photoallergic contact dermatitis and benzydamine is not part of most photoallergen series

Nicolau Livedoid Dermatitis following intramuscular benzathine penicillin injection

We report the case of a 64-year-old male presenting with a rapidly enlarging painful violaceous plaque in the left buttock and posterior thigh, following a gluteal intramuscular injection of benzathine penicillin. Associated urinary incontinence and lower left limb paresis were consistent with sciatic and lower sacral nerve damage, as confirmed by electromyography. Additional underlying muscular damage was observed in ultrasound and computer tomodensitometry scans and supported by high serum levels of creatine kinase and lactate dehydrogenase. Aggressive treatment was performed with fluid expansion, intravenous steroid bolus, vasodilators and anticoagulation, resulting in slow improvement of cutaneous and muscular lesions. However, no significant effect was observed on neurologic dysfunction after 6 months of regular neuromuscular rehabilitation. Nicolau Livedoid Dermatitis is a rare and potentially fatal condition showing variable levels of tissue impairment and unpredictable course and prognosis. Specific treatment is not consensual and the efficacy of any particular treatment remains to be established

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

PURPOSE: NOD2 mutations have been linked to an increased risk of Crohn's disease and to some of its phenotypes. The association between NOD2 mutations and susceptibility to ulcerative colitis (UC) remains somewhat controversial and potential correlations between these mutations and UC phenotype have not been studied. AIM: To assess whether NOD2 mutations are a risk factor for UC in Portugal and if there are any genotype-phenotype correlations in these patients. METHODS: The three main NOD2 mutations were searched in 200 patients with UC and in 202 healthy controls. RESULTS: NOD2 mutations were present in 28 patients with UC (14.0 %) and in 27 controls (13.4 %) (p = 0.853). Mutation carriers were more likely to receive steroids during the first year of disease than non-carriers (54.2 % vs. 29.6 %, p = 0.018) and among these patients the need for intravenous administration was more frequent in those with the R702W polymorphism (90.0 % vs. 45.5 %, p = 0.014). In patients with severe colitis admitted for intravenous steroids, a greater proportion of mutation carriers was considered intravenous-steroid refractory and required salvage therapy (90.0 % vs. 38.1 %, p = 0.004). Patients with NOD2 mutation were submitted to colectomy more frequently than non-carriers (17.9 % vs. 4.1 %. p = 0.015). No correlation with the need for immunosuppressants/immunomodulators was found. CONCLUSIONS: In the Portuguese population, NOD2 mutations do not increase the risk of UC but are associated with a more aggressive course including greater need of steroids in the first year, increased incidence of intravenous-steroid refractoriness and a higher colectomy rate

CARD15 mutations and colorectal cancer in a South European country

PURPOSE: CARD15 mutations are associated with higher susceptibility to Crohn's disease (CD) and longstanding colonic CD increases the risk of developing colorectal cancer (CRC). The relation between these mutations and sporadic CRC remains controversial. The aim of this study was to assess whether germline and/or somatic CARD15 mutations are risk factors for sporadic CRC in Portugal and whether there are genotype-phenotype correlations in these patients. METHODS: The three main CARD15 mutations (R702W, G908R and 3020insC) were researched in 112 sporadic CRC patients and 152 healthy subjects. RESULTS: Overall, CARD15 mutations were found in 18 patients (16.1%) and in 15 controls (9.9%; p = 0.132). Individually, the incidence of R702W was significantly higher in patients than in controls (12.5% vs. 5.3%, p = 0.035), whereas the genotype frequencies for G908R (2.7% vs. 3.3%) and 3020insC (0.9% vs. 1.3%) were not statistically different between the two groups. Entire genotypic agreement was found in patients genotyped for blood and neoplastic DNA. A significantly higher incidence of CARD15 mutations was detected in patients with CRC diagnosed under 60 years old (28.6% vs. 10.4%, p = 0.015) and in female patients (24.4% vs. 10.4%, p = 0.048). No associations were found between CARD15 mutations and family history, symptoms or CRC pathologic characteristics. CONCLUSIONS: The CARD15 R702W variant might be a predisposing factor to sporadic CRC in Portugal, particularly in patients under 60-years old and in female patients. This susceptibility appears to be linked with germline CARD15 mutations. Nevertheless, we have found no evidence that CARD15 mutations predict the pathologic characteristics of CRC

Removal of hexavalent chromium of contaminated soil by coupling electrokinetic remediation and permeable reactive biobarriers

PURPOSE: In this study, a novel and ecological alternative have been developed to treat soils contaminated with hexavalent chromium coupling two well-known systems: electrokinetic remediation and permeable reactive biobarriers. The electric field promotes the electromigration of the hexavalent chromium oxyanions towards the anode. The biobarriers were placed before the anode electrode, in order to promote the reduction and retention of the chromium migrating in its direction. Thus, this technology provided a global treatment to soil removal without subsequent treatments of the contaminated effluents. METHODS: The electrokinetic system was coupled with two different permeable reactive biobarriers composed by Arthrobacter viscosus bacteria, supported either in activated carbon or zeolite. An electric field of 10 V was applied and two different treatment times of 9 and 18 days were tested. RESULTS: Removal values of 60% and 79% were obtained when electrokinetic treatment was coupled with zeolite and activated carbon biobarriers, respectively, for a test period of 18 day. The reduction of hexavalent chromium to trivalent chromium was around 45% for both systems. CONCLUSIONS: In this work, two types of biobarriers were efficiently coupled to electrokinetic treatment to decontaminate soil with Cr(VI). Furthermore, the viability of the new coupling technology developed (electrokinetic + biobarriers) to treat low-permeability polluted soils was demonstrated.This work was supported by the Spanish Ministry of Science and Innovation (CTQ2008-03059/PPQ), Xunta de Galicia (08MDS034314PR). The authors are grateful to the Spanish Ministry of Science and Innovation for providing financial support for Marta Pazos under the Ramon y Cajal program and the Fundacao para a Ciencia e Tecnologia, Ministerio da Ciencia e Tecnologia, Portugal through the PhD grant of Bruna Fonseca (SFRH/BD/27780/2006)

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Automatic Estimation of Verified Floating-Point Round-Off Errors via Static Analysis

This paper introduces a static analysis technique for computing formally verified round-off error bounds of floating-point functional expressions. The technique is based on a denotational semantics that computes a symbolic estimation of floating-point round-o errors along with a proof certificate that ensures its correctness. The symbolic estimation can be evaluated on concrete inputs using rigorous enclosure methods to produce formally verified numerical error bounds. The proposed technique is implemented in the prototype research tool PRECiSA (Program Round-o Error Certifier via Static Analysis) and used in the verification of floating-point programs of interest to NASA